Why does space travel weaken the immune system?

Scientists from the University of Ottawa and The Ottawa Hospital have shown that the expression of (mostly protein-coding) genes in white blood cells changes rapidly when astronauts reach the International Space Station (ISS), which may explain why astronauts appear more susceptible to infectious diseases while in space. Their study, published in the journal Frontiers in Immunology, also showed that most genes returned to their typical pre-flight level of expression within a few weeks to one year after landing.

It is well known that astronauts on board the ISS commonly suffer from skin rashes, as well as respiratory and non-respiratory diseases. Astronauts are also known to shed more live virus particles, for example Epstein-Barr virus, varicella-zoster responsible for shingles, herpes-simplex-1 responsible for sores and cytomegalovirus. These observations suggest that our immune system might be weakened by space travel. But what could cause such an immune deficit?

The Ottawa researchers studied gene expression in leukocytes (white blood cells) in a cohort of 14 astronauts (three women and 11 men) who resided on board the ISS for between 4.5 and 6.5 months between 2015 and 2019. Leukocytes were isolated from 4 mL blood drawn from each astronaut at 10 time points: once pre-flight, four times in flight and five times back on Earth. The researchers found that 15,410 genes were differentially expressed in leukocytes.

Among these genes, the team identified two clusters, with 247 and 29 genes respectively, which changed their expression in tandem along the studied timeline. Genes in the first cluster were dialled down when reaching space and back up when returning to Earth, while genes in the second followed the opposite pattern. Both clusters mostly consisted of genes that code for proteins, but with a difference: their predominant function was related to immunity for the genes in the first cluster, and to cellular structures and functions for the second. These results suggest that when someone travels to space, these changes in gene expression cause a rapid decrease in the strength of their immune system.

“A weaker immunity increases the risk of infectious diseases, limiting astronauts’ ability to perform their demanding missions in space,” said Dr Guy Trudel, a rehabilitation physician and researcher at The Ottawa Hospital and professor at the University of Ottawa. “If an infection or an immune-related condition was to evolve to a severe state requiring medical care, astronauts while in space would have limited access to care, medication or evacuation.”

The authors hypothesised that the change in gene expression of leukocytes under microgravity is triggered by ‘fluid shift’, where blood plasma is redistributed from the lower to the upper part of the body, including the lymphatic system. This causes a reduction in plasma volume by between 10% and 15% within the first few days in space. Fluid shift is known to be accompanied by large-scale physiological adaptations, apparently including altered gene expression.

The good news is that most genes in either of the two clusters returned to their pre-flight level of expression within one year after return to Earth, and typically much sooner — on average, after a few weeks — meaning returning astronauts run an elevated risk of infection for at least one month after landing back on Earth. The authors do not yet know how long it takes before immune resistance is fully back to its pre-flight strength: this is likely to depend on age, sex, genetic differences and childhood exposure to pathogens.

“The next question is how to apply our findings to guide the design of countermeasures that will prevent immune suppression while in space, in particular for long-duration flight,” said Dr Odette Laneuville, an associate professor at the University of Ottawa and lead author of the study.

“The health of astronauts while in space, especially during long missions, would benefit from detecting both immune dysfunction and subclinical inflammation. Early detection provides opportunities for intervention, with the aim to prevent a progression towards severe symptoms.”

Image caption: Astronaut Thomas Pesquet inserts blood samples into the Minus Eighty-Degree Laboratory Freezer for ISS (MELFI). Image courtesy of NASA.